TMS 2026: Pauline Maki, PhD, discusses real-world OPTION-VMS data linking fezolinetant to improvements in menopausal VMS, depression, and anxiety symptoms.
Women receiving fezolinetant (Veozah; Astellas Pharma) for moderate to severe menopausal vasomotor symptoms (VMS) experienced significant improvements in hot flash and night sweat bother, as well as depressive and anxiety symptoms, according to preliminary findings from the phase 4 OPTION-VMS study presented at The Menopause Society 2026 Annual Meeting in San Diego, California.
In the real-world study, fezolinetant users experienced a least-squares (LS) mean reduction of 2.66 points in Menopause-Specific Quality of Life (MENQOL) VMS domain scores at week 12 (95% CI, −2.95 to −2.37; P<.001). Improvements were observed as early as week 4 and were accompanied by significant reductions in depressive and anxiety symptoms, suggesting potential benefits beyond VMS relief.
In an interview with Patient Care Online, presenting author Pauline Maki, PhD, professor of psychiatry, psychology, and obstetrics and gynecology at the University of Illinois Chicago College of Medicine, discussed the clinical implications of the findings, particularly for physicians managing menopausal VMS in women with co-occurring mood symptoms.
The ongoing, prospective, multicenter OPTION-VMS study (NCT06049797) is evaluating patient-reported outcomes among women aged 40 to 75 years prescribed nonhormonal therapies, including fezolinetant, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and other treatments such as gabapentin or oxybutynin.
Among 375 fezolinetant users, LS mean reductions at week 12 were 3.04 points on the 9-item Patient Health Questionnaire (PHQ-9; 95% CI, −3.63 to −2.45) and 2.44 points on the 7-item Generalized Anxiety Disorder scale (GAD-7; 95% CI, −3.00 to −1.89), both P < .001.
Maki emphasized that the improvements were particularly notable because participants generally reported mild depressive and anxiety symptoms at baseline, with average scores subsequently declining into the minimal symptom range.
“I was pretty astounded that not only did we see these beneficial effects, but we saw them on clinical instruments that are more sensitive to these depressive symptoms," Maki told Patient Care Online.
Although women receiving SSRIs/SNRIs also experienced significant improvements in mood symptoms, Maki cautioned that the observational study was not designed or powered to directly compare treatment groups. Whether the improvements associated with fezolinetant reflect a direct effect on mood or occur secondary to VMS relief remains unknown.
For primary care physicians, Maki suggested that these findings may broaden discussions around nonhormonal treatment selection, particularly when women present with both bothersome VMS and mild depressive or anxiety symptoms. However, fezolinetant is not approved to treat depression or anxiety, and the results should not be interpreted as establishing comparable efficacy to antidepressant therapy.
Maki also discussed the limitations of the preliminary findings, including the absence of randomization, a placebo group, and head-to-head comparisons. Longer-term follow-up from OPTION-VMS, including objective sleep outcomes, is expected to provide additional insight into the effects of nonhormonal menopause therapies.
Watch the interview above to hear Maki discuss the findings, how they may influence shared treatment decisions, and what clinicians should consider when interpreting these early real-world results.
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